Catheter Related - Gram Positive Bloodstream Infections

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00467272
• Collaborator: Cubist Pharmaceuticals LLC (Industry)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 66.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Primary Objective:

-Evaluate the clinical efficacy and safety of Daptomycin given for treatment of catheter-related bloodstream infections (CRBSI) due to gram positive bacteremia in the context of standard of care antimicrobial therapy consisting mainly of Vancomycin with or without initial treatment with beta lactam antibiotics.

Condition or Disease	Intervention/Treatment	Phase
Bloodstream Infection	Drug: Daptomycin	Phase 2

Detailed Description

THE STUDY DRUG:

Daptomycin is an antibiotic designed to treat a variety of bacterial infections that are difficult to treat.

STUDY TREATMENT:

If you are found to be eligible to take part in this study, you will be given daptomycin by vein over 30 minutes every 24 hours for at least 7-14 days, depending on the type of bacteria that you have.

The central venous catheter (CVC) will either be removed, or it will be exchanged over a guide wire. The decision to remove or exchange the CVC and timing of the placement of the CVC will be decided by your primary physician and the willingness of you to remove or exchange your infected CVC. This will be done within 96 hours after your first positive blood culture (first blood drawn that showed bacteria). A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

If the study doctor and/or your primary doctor suspects that you have a mixed infection (2 or more certain types of bacteria) or pneumonia, you will also be treated with different types of antibiotics, by vein or mouth, in combination with the study drug. These antibiotics may include aztreonam, cefepime, imipenem, meropenem, ciprofloxacin hydrochloride, bactrim, and/or amoxicillin/clavulanate (a combination antibiotic).

If you are discharged from the hospital before completing the study medication, arrangements will be made to provide infusions on an outpatient basis (by a nurse, yourself, or a family member). You and/or a family member will be taught (by a nurse) how to take the study medication at home. Before you are discharged from the hospital, you will receive the kits that include enough supplies for you and/or a family member to give daptomycin by vein. If medication will be given at home, a prescription will be given to you to pick up your medication from the pharmacy before you discharge from the hospital. If possible, your primary doctor may arrange for you to receive medication at the M. D. Anderson outpatient treatment center, or a nurse will be scheduled to visit you at home to give you the medication.

STUDY TESTS/PROCEDURES:

During each week of treatment, you will have the following exams/procedures performed once a week.

• You will have blood drawn (about 1 tablespoon) for routine tests. It may be drawn from the CVC, if the CVC is still in place. The CVC exit site will be examined at each visit until you have no more signs or symptoms of infection.

• You will also have blood drawn (about 1 tablespoon) for a blood culture every other day until it no longer shows signs of infection.

• You will be asked about any symptoms or illnesses that you may have experienced since your last visit.

LENGTH OF STUDY:

Participation on this study will last for no more than 60 days (about 2 months).

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Open-Label Study to Evaluate the Safety and Efficacy of Daptomycin in the Treatment of Catheter-Related Gram Positive Bloodstream Infections
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daptomycin Daptomycin 6 mg/kg intravenous (IV) every 24 hours for at least 7-14 days, depending on the type of bacteria.	Drug: Daptomycin; 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for SA and at least 7 days for enterococci and CNS, Corynebacterium, and Propionibacterium.; Other Names: Cubicin

Outcome Measures

Primary Outcome Measures

1. Clinical Response Within 48 Hours [Within 48 hours from initiating the study drug]

   Number of participants with clinical response within 48 hours from initiation of Daptomycin, estimated by Bayesian posterior credible interval. Clinical response defined as resolution of clinical signs and symptoms within 48 hours from initiating the study drug.

2. Clinical Response Within 7 Days [Within 7 days from initiating the study drug]

   Number of participants with clinical response within 1 week from initiation of Daptomycin, estimated by Bayesian posterior credible interval. Clinical response defined as resolution of clinical signs and symptoms within 7 days from initiating the study drug.

3. Microbiological Response Within 48 Hours [Within 48 hours from initiating the study drug]

   Number of participants with microbiological response within 48 hours from initiation of Daptomycin. Microbiological response defined as eradication of the microorganism from the bloodstream (negative blood cultures).

4. Microbiological Response Within 7 Days [Within 7 days from initiating the study drug]

   Number of participants with microbiological response within 7 days from initiation of Daptomycin. Microbiological response defined as eradication of the microorganism from the bloodstream (negative blood cultures).

Secondary Outcome Measures

1. Relapse [Within 3 months from initiating the study drug]

   Number of participants with relapse was defined as the recurrence of bacteremia within the first 3 months.

2. Number of Participants With Overall Response [Within 3 days from initiating the study drug]

   Overall response = symptom resolution within 3 days (since using antibiotic) + microbiological resolution within 3 days + no infection-related death + no infection-related late complications + no relapse. Infection-related late complication was defined as the development of deep-seated infection that was not present or suspected at the onset of bacteremia but was subsequently diagnosed after 1 week from initiation of study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or non-pregnant, non-lactating females with an age of greater than or equal to 18 years.

• The suspected culprit on exchangeable central venous catheter (CVC) is tunneled or non-tunnel (including ports and PICC) and antibiotic or non-antibiotic coated catheter inserted in the subclavian, jugular, peripheral or femoral vein.

• Patients must have at least two signs of sepsis from the list below, in any combination, within 48 hours prior to Daptomycin therapy and no other source for the bacteremia other than CVC: a. Core temperature =/>38.0 degrees C or =/<36.0 degrees C, measured orally, rectally, tympanic ally or via a central catheter. If auxiliary add 0.5 degrees C to the measured temperature; b. Pulse rate =/> 100 beats/min.; c. Respiratory rate =/> 20/min.; d. white blood cell (WBC) count =/>12,000/mm^{3 or =/<4,000/mm}3 differential count showing >10% band forms; e. Systolic blood pressure =/<90 mm Hg.

• Patients with probable or definite diagnosis of uncomplicated CVC-related gram positive bacteremia that includes at least one positive blood culture for Coagulase Negative Staphylococci (CNS), Staphylococcus aureus (SA), Enterococci, Corynebacterium, and Propionibacterium (If the positive blood culture is drawn through the CVC for skin flora such as CNS, Corynebacterium, Propionibacterium, Micrococcus and Bacillus, then at least >15 colonies/ml will be required or the time of positive (DTP) of CVC at least 2 hours earlier than the peripheral culture).

• Signed informed consent.

• No apparent source for the clinical manifestation of bacteremia other than the catheter (may have local signs and symptoms at the catheter site).

Exclusion Criteria:

• Estimated Serum Creatinine Clearance <30 mL/min (according to Cock-Gault-formula)at the time gram positive bacteremia was diagnosed unless the patient is on dialysis.

• Bilirubin >4 times the upper limit of normal at the time gram positive bacteremia was diagnosed.

• Treatment with an antibiotic, such as vancomycin, linezolid, tigecycline or daptomycin, effective against resistant gram positive bacterial infections, such as methicillin resistant staphylococci, for more than 48 hours within 72 hours of study medication initiation, unless treatment failed that is defined as a persistent fever, leukocytosis, and/or repeated positive blood cultures (CVC and peripheral) for 72 hours or longer of appropriate antibiotics treatment other than Daptomycin.

• Documented gram positive bacteremia within last 1 month due to source other than CVC.

• Patients who have participated in another investigational anti-infective study within 30 days.

• History of hypersensitivity to lipopeptides.

• Presence of additional source of infection with same organism cultured from blood, eg. endocarditis (as evidenced by vegetations on an echocardiogram), septic thrombosis.

• Conditions with markedly decreased albumin in plasma (<1.5 g/dl), e.g., cirrhosis, nephritic syndrome, end-stage renal disease.

• Prosthetic valve.

• Oliguria defined as urine output of <20 cc/hour averaged over 24 hours.

• Possible complicated CRBSI with persistent bacteremia for more than 48 hours on active antimicrobial therapy (such as osteomyelitis, endocarditis, and septic thrombosis).

• Patients with diagnosis of pneumonia that is due to S. aureus organism, e.g, S. aureus from sputum or bronchial cultures.

• creatine phosphokinase (CPK) >10 times max-normal in asymptomatic patients and CPK >5 max-normal in symptomatic patients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Cubist Pharmaceuticals LLC

Investigators

• Principal Investigator: Issam Raad, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Official Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00467272
• Other Study ID Numbers: 2006-0958
• First Posted: Apr 30, 2007
• Last Update Posted: Feb 8, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by M.D. Anderson Cancer Center: Catheter-Related Bloodstream Infections; Bloodstream Infection; Daptomycin; Cubicin; CRBSI
• Additional relevant MeSH terms: Infections; Communicable Diseases; Sepsis; Daptomycin

Study Results

Participant Flow

Recruitment Details	Recruitment Period: June 2006 to March 2008. All recruitment done at UT MD Anderson Cancer Center.
Pre-assignment Detail	This study is the continuation of trial NCT00507247 which included 11 participants; the results has been combined NCT00507247 and NCT00467272. A total of combined participants were 41, out of which 38 participants were included in the analysis and 3 participants were excluded.

Arm/Group Title	Daptomycin 6 mg/kg IV
Arm/Group Description	Daptomycin: 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for Staphylococcus aureus (SA) and at least 7 days for enterococci and Coagulase Negative Staphylococci (CNS), Corynebacterium and Propionibacterium.
Period Title: Overall Study
STARTED	41
COMPLETED	38
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Daptomycin 6 mg/kg IV
Arm/Group Description	Daptomycin: 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for Staphylococcus aureus (SA) and at least 7 days for enterococci and Coagulase Negative Staphylococci (CNS), Corynebacterium and Propionibacterium.
Overall Participants	38
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	13 34.2%
Male	25 65.8%
Region of Enrollment (participants) [Number]
United States	38 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Response Within 48 Hours
Description	Number of participants with clinical response within 48 hours from initiation of Daptomycin, estimated by Bayesian posterior credible interval. Clinical response defined as resolution of clinical signs and symptoms within 48 hours from initiating the study drug.
Time Frame	Within 48 hours from initiating the study drug

Outcome Measure Data

Analysis Population Description

Of the 38 participants analyzed, one participant was excluded from the analyses because the date of symptom resolution was missing.

Arm/Group Title	Daptomycin 6 mg/kg IV
Arm/Group Description	Daptomycin: 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for Staphylococcus aureus (SA) and at least 7 days for enterococci and Coagulase Negative Staphylococci (CNS), Corynebacterium and Propionibacterium.
Measure Participants	37
Count of Participants [Participants]	28 73.7%

2. Primary Outcome

Title	Clinical Response Within 7 Days
Description	Number of participants with clinical response within 1 week from initiation of Daptomycin, estimated by Bayesian posterior credible interval. Clinical response defined as resolution of clinical signs and symptoms within 7 days from initiating the study drug.
Time Frame	Within 7 days from initiating the study drug

Outcome Measure Data

Analysis Population Description

Of the 38 participants analyzed, one participant was excluded from the analyses because the date of symptom resolution was missing.

Arm/Group Title	Daptomycin 6 mg/kg IV
Arm/Group Description	Daptomycin: 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for Staphylococcus aureus (SA) and at least 7 days for enterococci and Coagulase Negative Staphylococci (CNS), Corynebacterium and Propionibacterium.
Measure Participants	37
Count of Participants [Participants]	33 86.8%

3. Primary Outcome

Title	Microbiological Response Within 48 Hours
Description	Number of participants with microbiological response within 48 hours from initiation of Daptomycin. Microbiological response defined as eradication of the microorganism from the bloodstream (negative blood cultures).
Time Frame	Within 48 hours from initiating the study drug

Outcome Measure Data

Analysis Population Description

Of the 38 participants analyzed, one participant was excluded from the analyses because the date of microbiological eradication was unknown.

Arm/Group Title	Daptomycin 6 mg/kg IV
Arm/Group Description	Daptomycin: 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for Staphylococcus aureus (SA) and at least 7 days for enterococci and Coagulase Negative Staphylococci (CNS), Corynebacterium and Propionibacterium.
Measure Participants	37
Count of Participants [Participants]	29 76.3%

4. Primary Outcome

Title	Microbiological Response Within 7 Days
Description	Number of participants with microbiological response within 7 days from initiation of Daptomycin. Microbiological response defined as eradication of the microorganism from the bloodstream (negative blood cultures).
Time Frame	Within 7 days from initiating the study drug

Outcome Measure Data

Analysis Population Description

Of the 38 participants analyzed, one participant was excluded from the analyses because the date of microbiological eradication was unknown.

Arm/Group Title	Daptomycin 6 mg/kg IV
Arm/Group Description	Daptomycin: 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for Staphylococcus aureus (SA) and at least 7 days for enterococci and Coagulase Negative Staphylococci (CNS), Corynebacterium and Propionibacterium.
Measure Participants	37
Count of Participants [Participants]	34 89.5%

5. Secondary Outcome

Title	Relapse
Description	Number of participants with relapse was defined as the recurrence of bacteremia within the first 3 months.
Time Frame	Within 3 months from initiating the study drug

Outcome Measure Data

Analysis Population Description

Of the 38 participants analyzed, one participant was excluded from the analyses because of microbiological failure.

Arm/Group Title	Daptomycin 6 mg/kg IV
Arm/Group Description	Daptomycin: 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for Staphylococcus aureus (SA) and at least 7 days for enterococci and Coagulase Negative Staphylococci (CNS), Corynebacterium and Propionibacterium.
Measure Participants	37
Count of Participants [Participants]	3 7.9%

6. Secondary Outcome

Title	Number of Participants With Overall Response
Description	Overall response = symptom resolution within 3 days (since using antibiotic) + microbiological resolution within 3 days + no infection-related death + no infection-related late complications + no relapse. Infection-related late complication was defined as the development of deep-seated infection that was not present or suspected at the onset of bacteremia but was subsequently diagnosed after 1 week from initiation of study drug.
Time Frame	Within 3 days from initiating the study drug

Outcome Measure Data

Analysis Population Description

Of the 38 participants analyzed, one participant was excluded from the analyses because the date of symptom resolution was unknown.

Arm/Group Title	Daptomycin 6 mg/kg IV
Arm/Group Description	Daptomycin: 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for Staphylococcus aureus (SA) and at least 7 days for enterococci and Coagulase Negative Staphylococci (CNS), Corynebacterium and Propionibacterium.
Measure Participants	37
Count of Participants [Participants]	25 65.8%

Adverse Events

Time Frame	Adverse Events (AEs) and Serious Adverse Events (SAEs) were evaluated from the time of the first infusion of study drug through the end of the post-treatment visit, up to 2 years
Arm/Group Title	Daptomycin 6 mg/kg IV
Arm/Group Description	Daptomycin: 6 mg/kg IV every 24 hours for at least 7-14 days, depending on the type of bacteria. Treatment expected to be at least 14 days for Staphylococcus aureus (SA) and at least 7 days for enterococci and Coagulase Negative Staphylococci (CNS), Corynebacterium and Propionibacterium.
All Cause Mortality
	Daptomycin 6 mg/kg IV
	Affected / at Risk (%)	# Events
Total	4/38 (10.5%)
Serious Adverse Events
	Daptomycin 6 mg/kg IV
	Affected / at Risk (%)	# Events
Total	18/38 (47.4%)
Metabolism and nutrition disorders
Increased Creatinine kinase	18/38 (47.4%)
Skin and subcutaneous tissue disorders
Rash	18/38 (47.4%)
Other (Not Including Serious) Adverse Events
	Daptomycin 6 mg/kg IV
	Affected / at Risk (%)	# Events
Total	18/38 (47.4%)
Nervous system disorders
Confusion	18/38 (47.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.